Calcium Influx Inhibition is Involved in the Hypotensive and Vasorelaxant Effects Induced by Yangambin

Molecules

Islania Giselia Albuquerque Araújo⁴  Darizy Flávia Silva³  Maria do Carmo de Alustau⁴  Katy Lísias Gondim Dias¹  Karla Veruska Marques Cavalcante¹  Robson Cavalcante Veras⁴  José Maria Barbosa-Filho⁴  Mario dos Anjos Neto²  Lusiane Maria Bendhack²  Nadja de Azevedo Correia¹ 

[1] Departamento de Fisiologia e Patologia, Centro de Ciências da Saúde, Universidade Federal da Paraíba, Cidade Universitária, 58051-900 João Pessoa, PB, Brazil;Departamento de Farmacologia, Escola de Medicina de Ribeirão Preto, Universidade de São Paulo, postal code Ribeirão Preto, SP, Brazil;Laboratório de Neurociências, Instituto de Ciências da Saúde, Universidade Federal da Bahia, Avenida Reitor Miguel Calmon, Vale do Canela, 40110-902 Salvador, BA, Brazil;Laboratório de Farmacologia Cardiovascular, Centro de Biotecnologia, Universidade Federal da Paraíba, Cidade Universitária, 58051-900 João Pessoa, PB, Brazil

关键词: lignan;    yangambin;    mesenteric artery;    vasodilation;    calcium influx;   

DOI  :  10.3390/molecules19056863

来源: mdpi

【 摘 要 】

The pharmacological effects on the cardiovascular system of yangambin, a lignan isolated from Ocotea duckei Vattimo (Lauraceae), were studied in rats using combined functional and biochemical approaches. In non-anaesthetized rats, yangambin (1, 5, 10, 20, 30 mg/kg, i.v.) induced hypotension (−3.5 ± 0.2; −7.1 ± 0.8; −8.9 ± 1.3; −14 ± 2.3, −25.5% ± 2.6%, respectively) accompanied by tachycardia (5.9 ± 0.5; 5.9 ± 1.6; 8.8 ± 1.4; 11.6, 18.8% ± 3.4%, respectively). In isolated rat atria, yangambin (0.1 µM–1 mM) had very slight negative inotropic (Emax = 35.6% ± 6.4%) and chronotropic effects (Emax = 10.2% ± 2.9%). In endothelium-intact rat mesenteric artery, yangambin (0.1 µM–1 mM) induced concentration-dependent relaxation (pD₂ = 4.5 ± 0.06) of contractions induced by phenylephrine and this effect was not affected by removal of the endothelium. Interestingly, like nifedipine, the relaxant effect induced by yangambin was more potent on the contractile response induced by KCl 80 mM (pD₂ = 4.8 ± 0.05) when compared to that induced by phenylephrine. Furthermore, yangambin inhibited CaCl₂-induced contractions in a concentration-dependent manner. This lignan also induced relaxation (pD₂ = 4.0 ± 0.04) of isolated arteries pre-contracted with S(−)-Bay K 8644. In fura-2/AM-loaded myocytes of rat mesenteric arteries, yangambin inhibited the Ca²⁺ signal evoked by KCl 60 mM. In conclusion, these results suggest that the hypotensive effect of yangambin is probably due to a peripheral vasodilatation that involves, at least, the inhibition the Ca²⁺ influx through voltage-gated Ca²⁺ channels.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.